Optical isomers are molecules which are made up of the same number and kind of atoms, and which have virtually identical physical properties and structure, except that they have different effects upon polarized light. Each individual isomer of a pair of optical isomers has an equal and opposite effect on polarized light, that is, each isomer causes the plane of polarized light to rotate to the same degree but in the opposite direction. This rotation of the plane of polarized light is known as optical rotation, and a molecule which causes optical rotation is said to have optical activity.
The existence of optical isomers is explained by the three-dimensional spatial configuration of carbon atoms. A carbon atom with four attached substituent groups has a tetrahedral structure. If all of the four substituents are different, the carbon atom is said to be asymmetric or chiral. This indicates that the molecule as a whole is asymmetric.
An asymmetric molecule may have two different geometrical configurations. The two configurations are nonsuperimposable mirror images. Nonsuperimposable mirror image structures of an asymmetric molecule are called enantiomers.
Enantiomers have identical physical properties, except that they rotate a plane of polarized light in opposite directions. An enantiomer which rotates a plane of polarized light in the clockwise direction--as determined by an observer facing the emerging beam of light--is dextrorotatory. The sign of rotation is taken as positive. The letter, d, standing for dextro- , and the notation (+), standing for positive rotation, are used interchangeably to designate a dextrorotatory enantiomer. An enantiomer which rotates the plane of polarized light in a counterclockwise direction is called levorotatory and the letter, 1, standing for levo- , or the notation (-), is used to designate the levorotatory enantiomeric form.
Quantitative measurements of the optical activity of asymmetrical compounds are usually reported as specific rotation, denoted by the symbol [.alpha.]. Specific rotation is defined by the following equation: ##EQU1## When specific rotations of pure liquids are reported, the density of the liquid replaces the concentration term in the equation. If the measurement is made with a pure liquid of unknown density, the result is reported as .alpha. (no bracket).
If the variables in the denominator of the above equation are kept constant, the observed rotation is characteristic of the optical isomer examined. Generally, the symbols [.alpha.] and .alpha. are accompanied by a subscript which indicates the wavelength of the light source used in the measurement, most often the D line of sodium (589 nm), and a superscript which indicates the temperature at which the measurement was performed, often 25.degree. C. The rotational value is preceded by a positive or negative sign indicating the direction of the rotation.
The specific rotation of an optical isomer may be measured in a device called a polarimeter. Such a device contains a means for converting ordinary light into plane polarized light, such as a Nicol prism, and a means for assessing the extent of rotation of the plane of polarized light after it has been passed through a sample solution of the optical isomer.
As explained, the d or (+) and the 1 or (-) notation refers to a physical property of an isomer--the direction in which the isomer causes a plane of polarized light to rotate. The actual geometric configuration of the isomers, however, is signified by a different notation. It is designated by the letters D or L or R and S. Unfortunately, no simple relationship exists between the sign of rotation and the configuration of the isomer. Hereinafter, to distinguish between optical isomers, the form of notation signifying the geometric configuration of the isomer will be used.
A mixture containing equal amounts of two enantiomers is called a racemate or a racemic mixture. Predictably, such mixtures do not rotate polarized light. The clockwise and counterclockwise rotation cancel out.
Ordinarily mixtures of enantiomer usually are perfectly racemic (equimolar amounts of each optical isomer). Under some circumstances, however, one enantiomeric form will be present in excess. The enantiomeric excess (ee) of an isomeric form is designated by a value of from 0 to 100%. Perfectly racemic mixtures have an ee value of 0%; a pure solution of one enantiomeric form has an ee value of 100%.
Racemic mixtures may be formed by converting an enantiomer of either the D or L form into a mixture of enantiomers. This process is called racemization. A common way of inducing racemization is by heating a solution of single enantiomer. Racemization can be monitored by observing the loss of optical activity in the solution over time.
In nearly all chemical procedures for the synthesis of asymmetric compounds, the product is a racemic mixture of the optically active forms, rather than an individual optically active isomer.
It is often important to isolate one optical isomer because in many cases, only one of the optical isomers possesses the biological or other functional activity. In order to obtain the biologically or functionally active isomer in substantially pure form, without the presence of the non-active isomer, the D and L isomers must be separated from each other.
The separation of a racemic mixture into its individual enantiomers is termed resolution. There are several existing methods for resolving racemic mixtures. The simplest, but most tedious and only occasionally applicable, is manual separation. Its application is restricted to the few cases where isomers of like configuration crystallize together to form observably different asymmetric crystals. The D and L forms of sodium ammonium tartrate, for example, may be resolved by this procedure. Another method involves the use of an enzyme which selectively degrades one isomer in the mixture.
Hydroxy compounds have a wide variety of practical uses as pharmaceuticals, flavorings, agricultural chemicals and food additives. Some of the better known examples of such compounds are threonine, malic acid, tartaric acid, menthol, carnitine and the drugs, ephedrine, octopamine, epinephrine and phenylephrine. Many useful hydroxy compounds, including those listed, have at least one chiral carbon atom. These include compounds in which the hydroxy group is attached directly to the chiral carbon atom and those in which it is attached to a carbon atom other than the chiral carbon atom. These hydroxy compounds are assymmetric and may exist in either the D or L isomeric form. In most cases, only one optically active form is biologically active. Standard procedures for the chemical synthesis of such compounds yield racemic mixtures.
The amino acid threonine cannot be synthesized by the human body and is therefore called an "essential" amino acid. It must be acquired preformed in the diet. Consequently this essential amino acid is used widely as a food additive. However, only the L form of threonine is utilized by the human body; its counterpart D-threonine cannot be utilized and therefore lacks nutritive value. For this reason it is highly desirable to obtain L-threonine in pure form. This necessitates separation of the D and L enantiomers which are both formed in the standard chemical syntheses. Unfortunately the conventional techniques for the resolution of racemic mixtures of hydroxy compounds, some of which have been described, are laborious, time-consuming and relatively inefficient.